Method of reducing intraocular pressure using glycine

ABSTRACT

INTRAOCULAR PRESSURE OR INTRAOCULAR TENSION IS REDUCED IN PATIENTS, FOR EXAMPLE THOSE SUFFERING FROM GLAUCOMA OR PREOPERATIVELY TO REDUCE INTRAOCULR TENSION PRIOR TO CATRACT SURGERY, E.G. INTRACAPSUL CATARACT EXTRACTION SO AS TO FICILITATE THE OPERATIVE PROCEDURE, IS REDUCED ACCORDING TO THE INVENTION BY THE ADMINISTRATION TO THE PATIENT OF AN EFFECTIVE AMOUNT OF GLYCINE. THE GLYCINE CAN BE ADMINISTERED ORALLY OR BY INJECTION, ORAL ADMINISTRATION BEING PREFERRED.

United States Patent 3,644,643 METHOD OF REDUCING INTRAOCULAR PRESSUREUSING GLYCINE John C. Krantz, Jr., Gibson Island, Md., assiguor toUnimed, Inc., Morristown, NJ. N0 Drawing. Filed Oct. 13, 1969, Ser. No.865,946 Int. Cl. A61k 27/00 US. Cl. 424-319 3 Claims ABSTRACT OF THEDISCLOSURE Intraocular pressure or intraocular tension is reduced inpatients, for example those suffering from glaucoma or preoperatively toreduce intraocular tension prior to cataract surgery, e.g. intracapsularcataract extraction so as to facilitate the operative procedure, isreduced according to the invention by the administration to the patientof an effective amount of glycine. The glycine can be administeredorally or by injection, oral administration being preferred.

BACKGROUND OF THE INVENTION Excessive intraocular pressure occurs incertain abnormal eye conditions, particularly glaucoma. As a matter offact, glaucoma is often defined as a pathologic state in which theintraocular pressure is elevated, intermittently or constantly, to alevel which the eye cannot withstand without damage to structure orimpairment of function. Therefore, in the treatment of glaucoma it ismost desirable to reduce the intraocular pressure back to a normalstate.

It is also desirable for the ophthalmologist to try to lower oculartension not only in the medical treatment of glaucoma but also prior tosurgical treatment. Also, in the case of intracapsular cataractextraction it is desirable to reduce the intraocular pressure prior tothe surgery.

The most effective agent for this purpose is glycerin, which isgenerally administered in an amount of 1-2 gm./kg. of body weight, mixedwith an equal amount of water. However, patients, are unable to tolerateglycerin for more than two or three days because of gastric problemssuch as vomiting and nausea which is caused by it. Another drug whichhas been used for this purpose is acetazolamide, but this drug alsocauses vomiting or nausea and its use is therefore considerably limited.

This invention is therefore concerned with the provision of an efficientand safe agent for reduction of intraocular pressure, which agent can betaken over prolonged periods of time and which can be administered byinjection of orally.

SUMMARY OF THE INVENTION Generally speaking, the present inventionrelates to a method of reducing intraocular pressure, which comprisesadministering an intraocular pressure reducing effective amount ofglycine. The method of administration is preferably oral, thoughadministration by injection, for example intravenous administration, isalso suitable.

It is a primary object of the present invention to provide compositionsand treatments for reduction of introocular pressure with safety fromthe standpoint of lack of toxicity and lack of undesired side effects.

It is another object of the present invention to provide compositionsand treatments for reducing intraocular pressure permitting the usethereof in the treatment of glaucoma and other conditions requiringreduced intraocular pressure by oral administration of safe andeffective amounts of glycine which is substantially as ef- 3,644,543Patented Feb. 22, 1972 fective as glycerin without any of the undesiredside effects thereof.

Other objects and advantages of the present invention will be apparentfrom a further reading of the specification and of the appended claims.

Glycine is the common term for aminoacetic acid. It is classified as anon-essential amino acid based on its growth effect in rats, and it hasdemonstrated very little pharmacological activity, being used primarilyas a dietary supplement.

However, I have discovered that glycine is highly effective in reducingintraocular pressure, and in view of the fact that oral doses of glycineare well tolerated, with no adverse effects, the glycine can be usedover prolonged periods of time for situations wherein reduction ofintraocular pressure is desired.

The glycine may be administered in capsules, in tablets preparedtherefrom either alone or with a pharmaceutically acceptable carrier, orin solutions thereof, all of these for oral administration, and inaddition, solutions can be prepared for objection purposes.

The dosage may vary within rather wide limits, and the general dosagefor patients to effect reduction of intraocular pressure is from about25-100 grams per day, the most preferred dosage being about 50 grams perday. The unit dosage may be from about 5-50 grams, the preferred dosagebeing about 25 grams administered twice a day.

DESCRIPTION OF PREFERRED EMBODIMENTS The following examples are given tofurther illustrate the invention. The scope of the invention is not,however, meant to be limited to the specific details of these examples.

EXAMPLE 1 Gelatin capsules are filled with 10 grams each of glycine. Onecapsule administered orally three times a day constitutes an averagedaily dose for the reduction of intraocular pressure.

EXAMPLE 2 Tablets are prepared using normal tabletting procedure, eachtablet containing 12.5 grams of glycine. Two of the tablets twice a dayconstitutes an average dose for the reduction of intraocular pressure.For severe conditions two tablets given four times a day may beadministered.

EXAMPLE 3 The following describes oral administration of glycineevaluated in regard to its effect on the normal intraocular pressure ofthe rabbit.

Materials and methods Five male New Zealand albino rabbits, ranging inweight from 3.1 to 3.9 kg., were utilized for the study.

All intraocular pressure measurement were made with an Improved LawtonShioetz Tonometer, using a 5.5 gram weight. Six readings, 3 on each eye,were taken on all rabbits at each time interval. The average of these 6readings represented one intraocular pressure measurement. Tetracainehydrochloride, 0.5%, was used to anesthetize both eyes prior to eachseries of measurements.

A 61.25% (w./v.) suspension of glycine in distilled Water wasadministered, via stomach tube, to all 5 rabbits. Tragacanth (0.2%) wasused as the suspending agent. Each rabbit received 2.45 gm./kg. ofglycine in a volume dose of 4 ml./kg.

Three control and eleven treatment intraocular pressure measurementswere obtained for each rabbit. Control measurements were taken at 30, 15and minutes. Tonometric measurements after glycine administration weretaken every 30 minutes for the first 4 hours. Additional measurementswere taken at 5, 24 and 48 hours.

Results and discussion In Table 1 are listed the individual and meanintraocular pressure measurements before and after oral administrationof glycine. Also shown is the statistical analysis of variance betweenmeans values and the value of 4 minutes were significantly different (P5%) from the TABLE 1 Individual and mean intraocular pressuremeasurements before and after oral administration of glycine (2.45gmJkg.)

Difierence Rabbit (mm. Hg) lrom control Mean S. mean No. 1 No. 2 N o. 3N o. 4 No. 5 (mm. Hg) (mm. Hg)

l Denotes significant difference from control mean. Analysis ofvariance:

Source 01 Degrees of Sum of Mean F variation freedom squares squareratio Rabbits 4 423. 31 105. 83 Times 11 657. 95 59. 81 12. 49 Error 44210. 93 4. 79

Total 59 1, 292. 19 21. 90

Norn.-Least significant difierence between control and treatment meansat the 5% confidence level:

D=Qx7 Error mean square least significant difference between the controlmeans and treatment means at the 5% level of confidence.

As is evident from the data, glycine markedly decreased intraocularpressure in all rabbits. Within minutes after administration theintraocular pressure of the 5 animals had decreased an average of 6.1mm. Hg. The maximum effect was observed at 120 minutes, when thepressures averaged 10.4 mm. Hg below that of the control. At 5 hours themean intraocular pressure had returned to within 3.0 mm. Hg of thecontrol mean. Similar measurements, slightly' below original controlvalues, were also obtained at 24 and 48 hours after administration.

Statistical treatment of the data revealed that the mean intraocularpressures from 30 minutes through 240 No. obs/time What is claimedis: 1. Method of reducing intraocular pressure, which comprisesadministering to a patient requiring reduction 50 of intraocularpressure an effective amount of glycine.

References Cited Takagaki, Chem. Abst. vol. 59 (1963), p. 4399b. Kubenaet al., Chem. Abst. vol. 64 (1966), p. 203680.

60 SAM ROSEN, Primary Examiner

